The innate immune response is the first line of defence against microbial infections. In Drosophila, two major pathways of the innate immune system (the Toll- and Imd-mediated pathways) induce the synthesis of antimicrobial peptides (AMPs) within the fat body. Recently, it has been reported that certain cationic AMPs exhibit selective cytotoxicity against human cancer cells; however, little is known about their anti-tumour effects. Drosophila mxc^mbn1 mutants exhibit malignant hyperplasia in a larval haematopoietic organ called the lymph gland (LG). Here, using RNA-seq analysis, we found many immunoresponsive genes, including those encoding AMPs, to be upregulated in these mutants. Downregulation of these pathways by either a Toll or imd mutation enhanced the tumour phenotype of the mxc mutants. Conversely, ectopic expression of each of five different AMPs in the fat body significantly suppressed the LG hyperplasia phenotype in the mutants. Thus, we propose that the Drosophila innate immune system can suppress the progression of haematopoietic tumours by inducing AMP gene expression. Overexpression of any one of the five AMPs studied resulted in enhanced apoptosis in mutant LGs, whereas no apoptotic signals were detected in controls. We observed that two AMPs, Drosomycin and Defensin, were taken up by circulating haemocyte-like cells, which were associated with the LG regions and showed reduced cell-to-cell adhesion in the mutants. By contrast, the AMP Diptericin was directly localised at the tumour site without intermediating haemocytes. These results suggest that AMPs have a specific cytotoxic effect that enhances apoptosis exclusively in the tumour cells.

MicroRNAs (miRNAs) are involved in the regulation of important biological processes. Here, we describe a novel Drosophila miRNAs involved in aging. We selected eight Drosophila miRNAs, displaying high homology with seed sequences of aging‐related miRNAs characterized in other species, and investigated whether the over‐expression of these miRNAs affected aging in Drosophila adult flies. The lifespan of adults over‐expressing miR‐305, a miRNA showing high homology with miR‐239 in C. elegans, was significantly shorter. Conversely, a reduction in miR‐305 expression led to a longer lifespan than that in control flies. miR‐305 over‐expression accelerated the impairment of locomotor activity and promoted the age‐dependent accumulation of poly‐ubiquitinated protein aggregates in the muscle, as flies aged. Thus, we show that the ectopic expression of miR‐305 has a deleterious effect on aging in Drosophila. To identify the targets of miR‐305, we performed RNA‐Seq. We discovered several mRNAs encoding antimicrobial peptides and insulin‐like peptides, whose expression changed in adults upon miR‐305 over‐expression. We further confirmed, by qRT‐PCR, that miR‐305 over‐expression significantly decreases the mRNA levels of four antimicrobial peptides. As these mRNAs contain multiple sequences matching the seed sequence of miR‐305, we speculate that a reduction in target mRNA levels, caused by ectopic miRNA expression, promotes aging.

This paper describes an innovative technique, the gradient pattern analysis (GPA), for analysing spatially extended dynamics. The measures obtained from GPA are based on the spatio-temporal correlations between large and small amplitude fluctuations of the structure represented as a dynamical gradient pattern. By means of four gradient moments it is possible to quantify the relative fluctuations and scaling coherence at a dynamical numerical lattice and this is a set of proper measures of the pattern complexity and equilibrium. The GPA technique is applied for the first time in 3D-simulated molecular chains with the objective of characterizing small symmetry breaking, amplitude and phase disorder due to spatio-temporal fluctuations driven by the spatially extended dynamics of a relaxation regime.

Significance: Androgen plays essential roles for sex differentiation of external genitalia through regulating male-biased genes. Even females can differentiate into male-type external genitalia depending on the degree of androgenic exposure. However, the mechanisms underlying androgen responsiveness in females are poorly defined. Here, we demonstrate Sp1 regulates the enrichment of H3K27ac on androgen receptor-mediated regulatory elements in both males and females, indicating transcriptional competency for male-biased genes is conserved by Sp1 in both sexes. Compound-MafBmutant mice lacking a tissue-specific enhancer in theMafB3′ UTR show incomplete male-type external differentiation similar to female-type differentiation. These findings underscore the idea that transcriptional competency for male-biased genes is preserved in both sexes, thus helping define the potential sexual fate of external genitalia.